Method of noninvasively determining a patient&#39;s susceptibility to arrhythmia

ABSTRACT

A system and method for detecting a patient&#39;s susceptibility to arrhythmias and cardiac tissue abnormality is disclosed. The method consists of using a computer, a display, software loaded onto the computer that generates graphical user interfaces (GUIs), an electronic interface, and a plurality of electrodes. The electronics interface is in electronic communication with the computer, and further in electronic communication with the electrodes that are placed by self-adhesion at predetermined locations on a test subject. According to one aspect of the invention, the method enables a user, typically a medical professional, to initiate, with minimal input, certain diagnostic tests involving observing and analyzing a series of QRS complexes, some of which are biased by passively altering the impedance of the patient&#39;s body, and others of which are unbiased. The signals are then compared, and the differences are analyzed to detect a patient&#39;s susceptibility to arrhythmias and cardiac tissue abnormality.

CROSS-REFERENCE TO RELATED APPLICATION

[0001] This application is a continuation of application Ser. No.09/487,557, filed Jan. 19, 2000 which claims priority under 35 U.S.C.§119(e), to previously filed U.S. Provisional Application No.60/116,396, filed Jan. 19, 1999 and U.S. Provisional Application No.60/133,983, filed May 13, 1999, and co-pending application Ser. No.09/126,864, filed Jul. 31, 1998 now U.S. Pat. No. 6,129,678 issued Oct.10, 2000; and is also a continuation-in-part of Ser. No. 09/126,864,filed Jul. 31, 1998, the subject matter of which is incorporated hereinby reference.

FIELD OF INVENTION

[0002] The invention relates to the detection of patients'susceptibility to arrhythmias and, more particularly, to varioustechniques for improving the detection of signals to achieve this goal.

BACKGROUND OF THE INVENTION

[0003] There are various devices known in the art for monitoring heartfunction. Many of these devices typically function by analyzing signalssuch as an electrocardiogram signal, which can be representative ofheart function. There is a need to identify patients at high risk forlife-threatening arrhythmias.

[0004] Various means have been proposed for detecting patientsusceptibility to arrhythmias. U.S. Pat. No. 5,117,834 discloses onemethod by which pulses of electromagnetic energy are injected into apatient and the changes in the patient's electrocardiographic signalscaused by the injection are recorded. U.S. Pat. No. 5,351,687 is similarin concept to U.S. Pat. No. 5,117,834, but it describes the use of amagnetic sensor for use in detecting the cardiographic signals. U.S.Pat. No. 5,555,888 discloses various means for adapting andautomatically facilitating the assessment techniques and means similarto that shown in the above patents for determining patientsusceptibility to arrhythmias.

[0005] Other techniques which are used to analyze cardiac signals forsomewhat similar purposes include those known as t-wave alternans andsignal-averaged electrocardiograms. Each of these techniques is limitedin its application and utility by various factors which are overcomethrough use of the below-described inventions.

SUMMARY OF THE INVENTION

[0006] The present invention provides a system and method ofdetermining, through noninvasive means, a patient's susceptibility toarrhythmia. More specifically, this invention comprises variousimprovements to known innovations for optimizing detection of apatient's susceptibility to arrhythmias. This invention embodiesnumerous software and sequence improvements for applying this basictechnology.

[0007] Another purpose of this invention is to provide hardware andsignal analysis means for detecting, amplifying, or improvingrecognition of relevant signals.

[0008] Another purpose of this invention is to provide for improvedperformance lead sets and the software to promote ease of attachment andremoval from the patient and ease of connection of the lead system tothe hardware.

[0009] A further object of this invention is to provide new combinationsof electrode placement and use to promote better arrhythmiasusceptibility diagnosis.

[0010] A further object of this invention is to provide a reduction inthe size of necessary components to allow for hand-held systemdimensions.

[0011] A further object of this invention is to provide a means fordistinguishing between the signals from the X, Y, and Z directions aswell as previously unused directional components of very low-levelsignal data.

[0012] Another object of this invention is to supply means fordisplaying of a patient's waveforms and other data derived from thedetected signals, as well as to provide various interfaces tocommunicate the data between the patient and physician or health careprofessional.

[0013] It is a further object of this invention to provide signalartifact reduction, and to provide a single point connector for the setof leads.

[0014] Another object of this invention is to provide improved leadmaterials for improved performance, as well as an improved lead effectmodeling (LEM).

[0015] It is yet another object of this invention to provide amplifiercircuitry that minimizes amplifier saturation and optimizes fastrecovery.

BRIEF DESCRIPTIONS OF THE DRAWINGS

[0016]FIG. 1 depicts the broad overview of the invention, showing thepatient electronic interface computer.

[0017]FIG. 2 is an exemplary depiction of a patient showing possibleelectrode patient locations.

[0018]FIG. 3 is a more close-up view of the lead system, showing theconnector and attached electrodes.

[0019]FIG. 4 depicts the principal graphical user interface (GUI)generated by the computer and the software portion of the invention.

[0020]FIG. 5 is the principal GUI generated by the computer and softwareportion of the invention, with the testing menu engaged.

[0021]FIG. 6 is the “New Subject” GUI.

[0022]FIG. 7 is the “Acquisition” GUI.

[0023]FIG. 8 is the “Perform All Standard Protocols” GUI.

[0024]FIG. 9 is the “Ready to Verify Sensing” GUI.

[0025]FIG. 10 is the “Acquisition Active” GUI generated by the computerand software portion of the invention.

[0026]FIG. 11 is the “Sensing Problem” GUI generated by the computer andsoftware portion of the invention.

[0027]FIG. 12 is the “Repeat Sensing Verification” GUI generated by thecomputer and software portion of the invention.

[0028]FIG. 13 is the principal GUI generated by the computer andsoftware portion of the invention, depicting a pulse graph.

[0029]FIG. 14 is the “Ready to Begin Testing Execution” GUI generated bythe computer and software portion of the invention.

[0030]FIG. 15 is the “Acquisition Active” GUI generated by the computerand software portion of the invention, depicting realtime R-waveacquisition.

[0031]FIG. 16 is the “Halted Data Acquisition” GUI generated by thecomputer and software portion of the invention.

[0032]FIG. 17 is the “Resume with Protocol” GUI generated by thecomputer and software portion of the invention.

[0033]FIG. 18 is the principal GUI generated by the computer andsoftware portion of the invention, depicting the “View” drop-down menuengaged.

[0034]FIG. 19 is the “Options” GUI generated by the computer andsoftware portion of the invention.

[0035]FIG. 20 is the “Simulator” GUI generated by the computer andsoftware portion of the invention.

[0036]FIG. 21 is the “QRS Status” GUI generated by the computer andsoftware portion of the invention.

[0037]FIG. 22 is the “Simulator” GUI generated by the computer andsoftware portion of the invention, depicting a further display option.

[0038]FIG. 23 is the “Simulator” GUI generated by the computer andsoftware portion of the invention, depicting a further display option.

[0039]FIG. 24 is the “Simulator” GUI generated by the computer andsoftware portion of the invention.

[0040]FIG. 25 is the “Simulator” GUI generated by the computer andsoftware portion of the invention.

[0041]FIG. 26 is the principal GUI generated by the computer andsoftware portion of the invention, depicting the “Data” drop-down menuengaged.

[0042]FIG. 27 is the “Accessing Stored Subject Data” GUI generated bythe computer and software portion of the invention.

[0043]FIG. 28 is the “Open” GUI generated by the computer and softwareportion of the invention.

[0044]FIG. 29 is the “Protocol Steps” GUI generated by the computer andsoftware portion of the invention.

[0045]FIG. 30 is the “Select Protocol Step” GUI generated by thecomputer and software portion of the invention.

[0046]FIG. 31 is an exemplary EKG signal.

[0047]FIG. 32 is a block diagram of switching and clamping circuit ofthe electronic interface.

[0048]FIG. 33 is a flow chart showing the overall interaction of theinvention.

[0049]FIG. 34 is a more detailed view of the connector and attachedleads, showing pin layout.

[0050]FIG. 35 is a block diagram of the isolated driver and shuntingswitch, a portion of the electronics interface.

[0051]FIG. 36 is an exemplary series of QRS complexes.

[0052]FIG. 37 is a high-level block diagram of the electronicsinterface.

[0053]FIG. 38 is a wire-level depiction of the electronics interface.

[0054]FIG. 39 is a flow chart/block diagram of the isolated fastrecovery EKG amplifier.

[0055]FIG. 40 is a schematic of the fast-recovery EKG amplifier.

[0056]FIG. 41 is a block diagram/flow chart of the isolated driversection of the electronics interface.

[0057]FIG. 42 is a schematic of the isolated driver section of theelectronics interface.

[0058]FIG. 43 is a high-level flow chart of the operation of thesoftware.

[0059]FIG. 44 is a lower-level flow chart of the test control andacquisition portion of the software.

[0060]FIG. 45 is a lower-level flow chart of the post-processingsoftware operation.

[0061]FIG. 46 is a lower-level flow chart of the realtime enter ofcontrols implemented by the software.

[0062]FIG. 47 is a data set of observed data.

[0063]FIG. 48 is a data set of observed data.

[0064]FIG. 49 is a data set of observed data.

[0065]FIG. 50 is a data set of observed data.

[0066]FIG. 51 is a data set of observed data.

[0067]FIG. 52 is a data set of observed data.

[0068]FIG. 53 is a data set of observed data.

[0069]FIG. 54 is a data set of observed data.

[0070]FIG. 55 is a data set of observed data.

[0071]FIG. 56 is a data set of observed data.

[0072]FIG. 57 is a data set of observed data.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0073] The invention provided is an improved method and system fordetecting patients' susceptibility to arrhythmia and cardiac tissueabnormality in a noninvasive fashion. In FIG. 1, computer 27 is operablycoupled to monitor 23, which is further closely coupled with electronicinterface 18 via wire 31. Lead system 12 is connected between patient 35and electronic interface 18.

[0074]FIG. 2 is a front and rear view of patient 35. In one preferredembodiment, lead system 12 consists of nine (9) lead wires.Advantageously, the lead system can be connected as shown in FIG. 2 forefficient and consistent setup of the invention. Typically, the leadsystem is preassembled with a predetermined number of leads havingpredetermined lengths. Although it is contemplated by this inventionthat the lead system can be preassembled with leads of different lengthsto accommodate different room sizes and patent locations, among otherfactors, a general consideration is that the sensing leads and energydelivery leads are less than 9 feet in length to reduce possible inducednoise. Further, the leads in lead system 12 are constructed from alow-impedance material, such as tin, sodium, silver, silver chloride, orother low-impedance material recognized as such by those skilled in theart. This construction assists in efficient delivery of subpacing energyfor stimulation leads and increased sensitivity for sensing leads. Theelectrodes involved with energy delivery are advantageously shaped andsized for placement on the patient's body habitus to minimize signalquality reduction by avoiding muscle tissue.

[0075]FIG. 3 shows a more detailed view of one preferred embodiment ofsingle-point connector 15 with 9 lead wires electronically coupledthereto. In this embodiment, each of the 9 lead wires is connected toone of 9 self-adhesive electrodes. The adhesive used on any specificelectrode can differ depending on various factors, including where onpatient 35 the electrode or patch is to be affixed and whether theelectrode is reusable or disposable. In one preferred embodiment,electrode 1 is to be connected in the correspondingly-numbered positionindicated in FIG. 2. Thus, for example, electrodes 1 and 2 are connectedon patient 35 at the corresponding left and right mid-axillary lines, ona horizontal plane, at the level where the fifth intercostal spaceintersects the sternum. Electrode 3 is placed on the sternum. In thisembodiment of the invention, electrode 4 is placed on patient 35 at thefifth intercostal space. Electrode 5 is a neck electrode and is attachedgenerally at the back of the neck, as indicated on back view 2.2 of FIG.2. Lead 6 is a left leg lead that will attach generally in the locationon patient 35, as shown on front view 2.1 of FIG. 2. The larger,rectangular electrodes, electrodes 7 and 8, are attached in the pectoralarea and back, respectively, as shown in FIG. 2. In one preferredembodiment, the generally pectorally-placed electrode 7, or patch, has askin contact surface area of at least 20 cm², and typically less thanabout 70 cm². The patches of lead system 12 can be constructed withdifferent electrical characteristics to facilitate energy transfer andsensing.

[0076] Single-point connector 15 is configured to electronically matewith electronic interface 18. A top-level block diagram of electronicinterface 18 is shown in FIG. 37. In one embodiment, single-pointconnector 15 advantageously couples 9 electroleads into one plugassembly. As can be seen in FIG. 3, one preferred embodiment is astacked lead receptacle having at least two rows of lead connectionsthat are identified with respect to each lead (also see FIG. 42). Thisadvantageously provides for a more compact connector, and provides forrapid and efficient coupling and decoupling to electronics interface 18.In one preferred embodiment, the connector 15 is designed to be easilyand rapidly coupled and decoupled with the electronics interface 18 bythe use of only one hand. Advantageously, this allows for efficientsetup and takedown of the invention. Patches 1 through 9 are premarked,as indicated on FIG. 3, to provide for simpler and more convenientplacement on patient 35. Further, the lead system 12 comprises areference lead 9. It is anticipated that the lead system 12 can be asingle-use system or a disposable system to provide for a safe andsterile means by which to perform the tests provided by this invention.Further, reusing the lead system may create a higher impedance in thesystem, which may make the lead system 12 more susceptible to noise. Inone preferred embodiment of the invention, a means is provided fordetermining whether the lead system has been previously used. This canbe done by using a single-use-type adhesive. Another means for detectingprevious use is creating a deformable tab on connector 15 that deformson its first mating with electronic interface 18, and thereafter is notusable. Creating fusible links or breakable tabs to indicate the leadsystem has been previously used are an additional means, among others.

[0077] The electronics interface 18, by coupling with computer 27,allows for the injection of low-level electromagnetic energy intopatient 35 to alter at least one cardiac signal. The energy is deliveredat a subpacing threshold and is typically introduced externally, throughthe patient's 35 chest and into cardiac tissue. The subpacing energy isdelivered just before a QRS complex event, as determined by the datagathered by the hardware and electronic interface 18, and as analyzed bythe software. Electronic interface 18 and attached computer 27 functionto process received signals, among other functions. The energy deliveryleads are typically leads 7 and 8; however, it is anticipated thatcircumstances may arise where more or less than two energy deliveryleads may be needed. In such cases, greater or fewer leads may beconfigured to delivery energy. Further, the number of sensing leads maybe variable as well, depending on the needs and judgment of the medicalprofessional administering the testing.

[0078]FIG. 31 depicts an exemplary QRS complex and related signals.P-wave 153 is the signal that typically precedes the actual QRS complex130. The interval between the start of the P-wave and the beginning ofQRS complex 130 is known as the PR interval 150. QRS complex 130 istypically made up of three distinct components: Q 117, which istypically the first negative signal; R 113, which is typically the firstpositive signal; and S 121, which is the first negative signalsubsequent to R 113 signal. T segment 133 is typically defined as themore-or-less flat signal, or absence of signal, subsequent to recoveryof the S 121 portion of QRS complex 130, prior to commencement oft-wave146. The QT interval is typically defined as the portion of the signalscommencing at the beginning of QRS complex 130 and ending after t-wave146. J Joint 137 is typically defined as the end of the QRS complex andthe beginning of the ST segment 133. The T-P interval (not indicated) isthe time period from the end of the T-wave to the beginning of the nextP-Wave. The entire cardiac cycle is P-Q-R-S-T.

[0079] The slight transcutaneous biosync or subpacing current istypically introduced by the invention at odd numbers of QRS complexnormal sinus beats. Resulting QRS complexes are then compared to theeven-numbered unbiased beats. By computer-implemented software, thedistinguishable signal differences can then be calculated and displayed.Generally, differences are found between the biased and unbiased QRScomplexes in patients with ventricular tachycardia and other indices ofarrhythmia or cardiac tissue abnormality. It is anticipated that theseinput potentials would be extremely small, for example, less than 100uV, and typically of a duration of less than about 100 mS. Such acurrent might involve visualization of a possible analog of latepotentials throughout the QRS complex.

[0080] Computer 27 operates a graphical user interface (GUI) basedsoftware, which generally includes a tool bar, a status bar, a displayarea, and various drop-down menus. The principal GUI is depicted in FIG.4. The GUI consists of display area 39, status bar 37, tool bar 42, anddrop-down menus 46. Tool bar 42 contains button icons that representshortcuts to many of the functions described below in association withdrop-down means 46. Status bar 37 depicts the general status 13 of thesoftware on the left-hand side, technical data 10 regarding the leadsensors and input current in the middle section, and frequency andprotocol information 28 generally on the right-hand side. FIG. 4illustrates a GUI in Microsoft Corporation's Windows 95® operatingsystem format. The GUI is generated by computer 27, which typicallyconsists of mouse 40, CPU 25, display 23, a keyboard (not shown)operably attached to computer 27, and peripheral input/output devices26, as well as storage media 21.

[0081]FIG. 5 depicts “Testing” drop-down menu 48 engaged. As revealed inFIG. 5, “Testing” drop-down menu 48 provides a series of options toperform testing provided for by this invention. If the “Performed TestSequence” 50 is selected, the GUI of FIG. 6 is generated on display 23.Using mouse 40 or keyboard input, a preexisting patient may be selectedfrom display area 39 of this GUI, or “New Patient” button 52 may beselected. Mouse 40 or keyboard input may be used to select all operablefunctions of the GUIs involved in this invention. If “OK” 36 is selectedfrom the GUI of FIG. 36, subject information 41 is retrieved for thehighlighted subject. “Cancel” 30 returns the operator to the view of theGUI of FIG. 4.

[0082]FIG. 7 depicts the informational GUI that appears if “New Patient”button 52 is selected. In the upper portion of the GUI represented inFIG. 7, subject information may be entered in box 44 which includesidentification number (ID) 55 to associate with the patient, patient'sName 58, patient's Birthdate 64, Gender 66 of the patient, Race 80 ofthe patient, and any miscellaneous notes 85 that might be helpful duringor after the patient's diagnostic sessions.

[0083] The lower portion of the GUI depicted in FIG. 7 includes sixboxes where testing parameters are entered. The test duration box 90 isconfigured by the medical professional to indicate how many QRS complexsignals will comprise the test. The options under the sensitivity inputbox 68 are low, medium, and high. This advantageously allows thesensitivity to be adjusted to correct over- or under-sensing caused bysubject-to-subject variation in QRS amplitude and morphology. The nextvariable parameter is the deviation limit 87, which is entered inmilliseconds in the correspondingly marked box. Deviation limit 87allows the operator to eliminate inaccurately-positioned stimulationsfrom post-processing. This can happen due to the predictive nature ofpre-R-wave stimulation and the normal R-R interval is variation (seeFIG. 36). The operator identifies the allowable tolerance. Any pulsesthat are greater than this tolerance are eliminated from furtherprocessing. Also in FIG. 7 is pulse configuration box 33. In pulseconfiguration box 33, the low-current pulse can be configured to accountfor the different circumstances of the patient to be tested. Theparameters or variables are current strength 72, width of the pulse 82(in milliseconds), and temporal location 92 of the pulse with respect tothe QRS complex. A one-millisecond Pulse Ramp Up 78 option is alsoavailable by checking the corresponding box on the GUI.

[0084]FIG. 8 depicts a GUI option screen where a simplified selectioncan be made for all available testing standard protocols. There,selection of “Yes” 11 invokes all currently defined standard protocols.These protocols are set up initially and invoke from this screen. Thisoption advantageously allows testing without requiring the operator toset the specific parameters for each subject being tested. “No” 17returns the user to the previously displayed GUI.

[0085]FIG. 9 is a GUI that appears on screen 23 to determine whether theprofessional is ready to verify the sensing of the electrodes attachedto patient 35. “Yes” 36 will commence the sensor verification. “Cancel”30 will return the operator to the previous screen. If default protocolsare to be used on the patient, then the operator need not define thetest parameters. The system will get these standard parameters from theinternal disk (not shown) of computer 27.

[0086] If “Cancel” 30 is selected on the GUI of FIG. 7, any changes willbe discarded and the performed test function will cease. If “OK” 36 isselected on the GUI of FIG. 7, the GUI of FIG. 8 will appear. Themedical professional will select “Yes” 11 if the system is to use thestandard protocol stored internally.

[0087] In a particular embodiment of the subject invention, prior toacquiring test data for a particular test, the computer-implementedsoftware will acquire data for a 10-second interval, displaying andindicating detected R-waves or QRS complexes (see FIG. 31). This processallows the operator to confirm the placement of lead system 12, and thesensitivity settings that appear in the GUI of FIG. 7. If the test datais not completely satisfactory to the operator, the steps represented inFIGS. 7, 8, 9, and 10 may be reiterated to allow the medicalprofessional to reposition the leads, if necessary, to provide foroptimal sensing and signal amplitude. During data acquisition, a windowdepicting the data being acquired appears. An exemplary display of thisgraphical depiction of acquired signal 47 appears in FIG. 10. After thetypical 10-second acquisition time, the GUI of FIG. 11 or FIG. 12 mayappear. The GUI of FIG. 12 gives the operator the opportunity foranother approximately 10-second data acquisition period. Ifsoftware-detected problems occur during data acquisition, a GUI such asthe one displayed in FIG. 11 may appear, notifying the operator ofpotential problems. These features give the operator more control overthe testing procedure, and advantageously provide for error control.

[0088] Typically, in one preferred embodiment of the invention, anauditory beeping occurs with R-wave acquisition. If no R-wave beepingoccurs or if poor signal amplitude is noted, adjustments in the leadsmay again be required, and sensing verification should be repeated viathe GUI of FIG. 12.

[0089] In situations where the operator is not performing standardprotocols, the system will allow the operator to interactively set thepulse position. FIG. 13 is a graphical depiction of pulse 59 on displayarea 39. Under these circumstances, the operator may use the cursor keyson the keyboard (not shown), coupled to computer 27 (not shown in FIG.13), to position the pulse location using an average of the QRS complexsignals received during sensing verification.

[0090] In one preferred embodiment, the final step in the performance ofthe test sequence function involves performing and recording the test.Prior to performing and recording the test, the software will representthe GUI prompt of FIG. 14. This will allow the operator to control thetiming of the test to ensure that both patient 35 and the operator areready to proceed.

[0091] When the “OK” 36 selection is made from the GUI of FIG. 14, theGUI of FIG. 15 is generated, graphically depicting the R-wave 34 inrealtime. If “Cancel” 30 is selected, the operator is returned to theprevious screen. The system is configured to emit an audible beepsynchronously with each R-wave sensed. As indicated on the GUI of FIG.15, pressing any key of the computer keyboard will halt the performancetest sequence. If a key is depressed during the test sequence, the GUInotification screen of FIG. 16 appears, notifying the operator what hasoccurred.

[0092] This invention anticipates that several other events may occurthat would halt acquisition, and similar GUIs to the GUI depicted inFIG. 16 will report such termination of the test procedure. For example,if R-wave sensing is indicated at a rate greater than 180 beats perminute, the test will automatically be halted. Further, if the inventionis having difficulty sensing the R-wave, or the R-wave is in any wayirregular, the test will be halted. If the test is interrupted duringthe execution of a test sequence, the sequence may be restarted at thebeginning of the interrupted test by selecting “Yes” 11 from the GUInotification screen of FIG. 17, which will be displayed after the testsequence is halted. Selecting “No” 17 from the GUI of FIG. 17 causes thesystem to return to the main menu screen of FIG. 4. If any of theremaining menu items in drop-down menu 48 are selected, a shortcut to apreviously-described procedure is executed. If “Quit” 19 (see FIG. 5)from Testing drop-down menu 48 is selected, the software program isclosed.

[0093]FIG. 18 shows the View drop-down menu 55 engaged. View drop-downmenu 55 provides access to functions required to select viewing optionsfor data acquired or loaded from disk. Each test performed by thesubject of the invention records 3 channels of data. The placement ofelectrodes (see FIG. 2) allows these signals to record far-field ECG inroughly orthogonal directions. It is recognized that the terms “ECG” and“ECG data” encompass electrocardiograms and similar data measured,generated, or reported by all means, including by use of the devices andmethods disclosed herein. Referring again to the electrode placement,this advantageously provides for a data representation that defines thesignal in three dimensions. Axes have been labeled X, Y, and Z. The Xsignal is recorded, for example, from left lead 1 to right lead 2, withleft lead 1 being the positive direction. The Y signal may be recordedfrom neck lead 5 to leg lead 6, with neck lead 5 being the positivedirection. The Z signal may be recorded from back lead 4 to sternum lead3, with back lead 4 being the positive direction. Other configurationsmay be possible, depending upon the judgment and needs of the patientand operator. In addition to the three required signals, at least twoadditional signals are preferably calculated. The X, Y, and Z signalsare combined to produce a magnitude and direction signal. A magnitudesignal can be used to detect signal variation independent of direction.A direction signal can be used to detect signal variation independent ofmagnitude. The upper portion of View drop-down menu 55 containsselectable options for each of the signals X 100, Y 102, and Z 104. Theoptions appear checked on the GUI when they are selected. Theseselections allow the medical professional to select which signals aredisplayed during certain viewing modes. The lower portion of thepull-down menu contains the viewing modes. Each mode allows the user toview the current data set in a different way. The viewing modes, as theyappear on dropdown menu 55, are “View Full Resolution,” 119, whichdisplays the X, Y, and Z signals at high resolution on monitor 23; “View2 Minute Screen” 123, which displays a selected signal compressed intotwo minutes per screen; and “View QRS Change” 125, which displays theselected signals with normal average, biased average, and differencedepictions. Selection of “Vector Angle” 139 displays the angularvelocity and direction change of the average signal. “Position BiasPulse” 111 displays the average of the selected signals, along with anindicator of pulse position. This advantageously allows interactivepositioning of stimulation by the medical professional performing thediagnostics.

[0094] “Signal Averaged ECG” 135 displays signal-averaged ECGinformation for normal, biased, and difference signals. Typically, inthe application of signal-averaged ECG 135, of primary importance to themedical professional is the flat area immediately following the QRScomplex, ST segment 133. ST Segment 133 is targeted because of its lackof signal in normal people (see FIG. 31). This lack of signal allows therecognition of the presence of very small-amplitude signals that canoccur in people with conduction problems indicative of a susceptibilityto arrhythmia or other cardiac tissue abnormality. Further, abnormalsignals may also exist within the QRS and be masked by thehigher-amplitude signal present there. Since this invention has theability to perform comparative analysis between stimulated andnon-stimulated beats, a much greater sensitivity may be achieved inareas where a higher natural signal is also present. Additionally, byexamining various areas of the QRS complex, information regarding sizeand position of conduction alteration may also be evident.

[0095] If “Options” 128 menu selection is made from View drop-down menu55, the GUI of FIG. 19 is displayed. “Option” 128, which is selectableby the GUI, is represented in FIG. 19. This function allows for betterinterpretation of the data accumulated. The “High-Pass Cutoff” option 60of the GUI in FIG. 19 can be set to use a fast-fourier transform (FFT),to filter out frequencies lower than those indicated prior to averaging.A zero setting disables high-pass filtering altogether. Low-pass cutoff94 uses an FFT to filter out frequencies higher than those indicatedprior to averaging. A setting of 1,000 disables low-pass filtering.Advantageously, lead effective modeling (LEM) can be selected in the GUIrepresented in FIG. 19. If LEM box 96 is checked, in a preferredembodiment, a 20 millisecond model of the impulse artifact isconstructed, based on the first four simulations. This model issubtracted from subsequent simulations to reduce artifact in thedisplayed information. Any voltage shifts created during stimulation arealso modeled and removed. LEM and this correction algorithm greatlyreduce artifact created by stimulation. A muscle response correctionalgorithm may also be implemented by the invention to advantageouslycorrect for signal artifacts during stimulation and acquisition cycles.Using this technique, stimulation is provided to the patient within anLEM time period between the T and P-waves, at the beginning andperiodically throughout the stimulation and acquisition process.Response to the stimulations is determined up to about 50 millisecondsfor each stimulation. LEM is then created by combining the response ofthe stimulations during this period to generate a response signal,whereafter the signal is used to mathematically attribute noisegenerated by electrical artifact and muscle activity. Also GUIselectable is a “60-Hz Notch FFT Filtering” 86 option, whichadvantageously filters out frequencies at the 60-Hz rate prior toaveraging. Accumulation Start time 88 and End time 89 can also be inputon the GUI indicated in FIG. 19. Accumulation Start time 88 controls thestarting range for the accumulated difference measurement on the averagescreen. The Accumulation End setting 89 controls the ending range forthe accumulated difference on the average screen. An exemplary result ofselecting “View Full Resolution” mode 119 is depicted in FIG. 20. Signalcharacteristics X 167, Y 173, and Z 177 are graphed independently.Again, status bar 37 indicates the various selected parameterspreviously discussed.

[0096] Individual QRS status may be determined from the GUI of FIG. 21.The various options in the QRS Status window 97 are as follows: if thestatus indicated is “Biased,” that means that the QRS complex has astimulation associated with it. If it is “Normal,” the QRS does not havean associated stimulation. The parameter “Valid” in status window 97means that the QRS has past selection criteria which is included in theaveraging. If the LEM stimulation is indicated (not shown), this meansthat the QRS complex is used for LEM. If “low correlation” is indicated(not shown) in status window 97, the QRS complex was too low and,therefore, was not used in the averaging. If there is a “Bad Interval”indication (not shown), then the preceding or following interval changedby greater than 300 milliseconds. If a “high-rate” status indication isindicated (not shown), the pulse rate exceeded 180 beats per minute andthe QRS complex was not used in the averaging. If “manual exclusion” isindicated (not shown), that means that the QRS complex was manuallyexcluded by the operator. If “Bad pulse Positioning” is indicated (notshown), the pulse position exceeded the tolerance set by the medicalprofessional or the default tolerance. Further, it is possible tomanually include or exclude a particular QRS from the averagingstatistics by using the “Include” 162 and “Exclude” 168 selectionbuttons on the GUI of FIG. 21. A previous QRS complex may be viewed byselecting the “prior QRS” button 142. The next QRS complex can be viewedby the selection of the “Next QRS” button 143.

[0097] An exemplary result of selecting “View 2 Minute Screen” 123 isdepicted in FIG. 22. The 2 Minute Screen mode allows the medicalprofessional to view a selected channel in an overview mode. In thismode, a two-minute portion of the selected channel 138 is displayed ondisplay area 39. R-wave correlation points and stimulation points areindicated on the display area of FIG. 20. R-wave correlation points arelonger, white indications (not shown) above the waveform. Stimulationpoints are red indications (now shown) below the waveform. Note thatboth Full Resolution 119 and View 2 Minute Screen 123 modes display thecurrent start and end time for the displayed portion of the test onstatus bar 37 at the bottom of the relevant GUI. Advantageously, as theoperator scrolls through the data, these values change to indicate theportion of data currently being displayed.

[0098] An exemplary result of selecting “View QRS Change” 125 mode isdepicted in FIG. 23. In FIG. 23, the upper graph 61 shows the average ofall nonbiased QRS complexes. The middle graph 65 shows the average ofall biased or stimulated QRS complexes. The lower graph 67 is thedifference graph that shows the difference between the normal and biasedwaveforms. Statistics identifying the accumulated area under each curveare displayed on the right. A double-end arrow 33 on the lower graphindicates the range over which the statistics were generated. The endpoints can be adjusted in the view options window. The Difference graphcontains cumulative Difference results along the bottom of each 10millisecond region, based on the magnitude signal. FIG. 24 depicts theVector Angle GUI. Vector Angle mode displays angular information 151 notreflected in the magnitude signal. The Vector angle mode displayschanges in the direction of the electrical signal, whereas the Magnitudemode displays changes in the amount of electrical signal.

[0099] When the Signal Averaged ECG menu selection is made from Viewdrop-down menu 55, the GUI of FIG. 25 is displayed on computer screen23. The various graphs represent the Signal Averaged information for theNormal 43 and Biased 44 QRS complexes, along with the Difference 45between the two. Standard QRS, LAS 40 and RMS 40 calculations can bemade. Noise threshold is displayed along with the standard deviation ofthe noise, as can be seen on the GUI of FIG. 25.

[0100] Another drop-down menu 46 is the Data drop-down menu 58. Datadrop-down menu 58 provides access to functions required for loadingpreviously acquired data from storage, such as a hard disk located incomputer 27, or from removable storage, such as a Zip™ disk or otherremovable storage media. Configuration of protocol steps is alsosupported here, along with typical backup and restore functions.

[0101]FIG. 27 is a GUT depiction of an exemplary menu for stored data.The date 16 and time 20 of acquisition, the identification 38, name 32,age 53, gender 54, bias information 63, R-wave sensitivity, and validcount 71 are all identified for reference, as can be noted in the upperarea 14 as depicted in FIG. 27. Selecting “Load From Internal Disk”option 126 from drop-down menu 58 reveals the GUI depicted in FIG. 28.The GUI of FIG. 28 depicts a variety of test data 57 that can beselected.

[0102] If “Load Protocol Step” 131 is selected from the drop-down menu,the GUI of FIG. 29 is displayed. This function loads an identifiedprotocol step 69 into the current test configuration. The GUI dialog boxallows the operator to identify the protocol step to load. Currentpatient information is not changed. To select a test configuration as aprotocol step, the GUI of FIG. 30 is used. The protocol step is enteredinto “Select Protocol Step” window 158 of the GUI, and “OK” 36 isselected to save the step.

[0103] Selection of “Restore” 114 from Data drop-down menu 58 restoresdata from an external media, such as a Zip™ disk, back to the internalhard drive of computer 27. Further, using the “Export” 195 command, datacan be exported to certain spreadsheet software programs.

[0104] The “Append To Stats” option 163 can be selected to append thestatistics of the current configuration parameters to the file.Advantageously, this option allows all test data sets in the currentdrive and directory to be processed using the current processingparameters and appended to the selected text, or .TXT, file. This usefuloption allows for batch processing and results based on alteredsettings.

[0105] Another menu 46 is Help drop-down menu 60. Full index and searchcapabilities of Help information is available. Further, on-line help,such as information gatherable through the Internet, is alsoanticipated.

[0106] A high-level operator flow chart for the software described aboveappears in FIG. 43. A typical embodiment of the method of using thesoftware begins at the Attach Leads To Patient stage 280. As describedabove, the operator will then Invoke Testing 282 and Input PatientInformation 284. If only a single test is desired, path 287 is taken,wherein the operator has a chance to Define Test Parameters 291.Otherwise, the operator has the choice of selecting All Tests Desired289 and proceeding directly to Verify Sensing 293. If Verify Sensing 293is Bad 295, then the lead positioning can be adjusted 297, and theverified sensing retried 294. Once the sensing is Good 198, the testparameters are loaded and the test is performed 288. Once the test iscompleted 292, there is a chance for the operator to see if more testsneed to be performed 296. If “Yes” 290, then the next predefined testsare loaded 286, and the operator is returned to Test Parameters Loadedand Test is Performed 288. If no further tests are to be formed at the296 state, the “No” path 299 is selected and the test is completed andleads are disconnected 300.

[0107]FIG. 44 is a depiction of the test control and data acquisitionsoftware flow chart. Raw data received from lead system 12 is receivedat the Realtime Test Control and Monitor Software 310, along withRealtime R-Wave Indicators 306. Realtime Test Control and MonitorSoftware 310 then controls and relays this information to generate GUIsto make a realtime display 312 on monitor 23. Inputs from the controlsystem can control other test features, as well, such as User AbortControl 304 and the user's ability to perform Test Configuration 308.Realtime Test Control and Monitor Software 310 can also send the RawData 303 to storage 313, and save Subject & Test Information 315.

[0108]FIG. 45 depicts the software flow charts of the post-processingsoftware. Annotation and post-processing control 332 controls ViewOptions 325 as described above, and subject and test informationretrieval from storage 320. Raw data from storage 326 is retrieved andanalyzed for R-wave detection 332. If LEM generation 330 is requested,then LEM Correction 334 will be performed, and Correlated QRS Alignment336 performed. Then, one to typically four processing options may beselected. Average Processing 340 can be selected for the data to beanalyzed after being filtered through filtering process 338. Then theoptions of displaying 350 or saving 355 the data are available. Ifvariance processing 342 is selected, the results may be displayed 350 orsaved 355. Similarly, if Power Spectrum Processing 344 is selected, theresults may be displayed 350 and/or saved 355. Also, Direction VectorProcessing 346 may be selected and, again, the resulting information canbe displayed 350 and/or saved 355.

[0109]FIG. 46 displays the lower-level flow diagram, more particularly,the stimulation timing software and the switch, shunt, relay, andstimulation control features that allow for efficient subpacingstimulation signals to be timely and efficiently administered, as wellas to facilitate the ability of the invention to make fast recovery toprepare for the next QRS complex event. Raw Data Stream 370 is filteredby Filters 368 and is sent to Realtime LEM Generator 360, and anyrealtime LEM correction is made at 366. Realtime R-wave detection isdetermined at step 364; and, if detected, the realtime R-waveindications are passed on at 362. Realtime R-Wave Detection 364 is alsolinked with the Stimulation Timing Software 352 that determines thetiming of the subpacing electrical pulse. Stimulation Timing Software352 interacts with the switch on the relay and the stimulation controlportion of the software 358. The computer interconnects to theelectronic interface as shown at 372.

[0110]FIG. 36 depicts an exemplary series of QRS complexes 130, orR-wave events. As can be seen, interval 144 is defined by that intervalfrom the beginning of one QRS complex to the beginning of the next QRScomplex. During the testing provided by this invention, a Pulse-DeliveryPoint 110 is determined by the invention, and a subpacing current isdelivered, typically as shown in FIG. 36. There is then the anticipatedR-wave 115, based upon two previous R-waves. In one preferredembodiment, the response to the stimulation is determined for a periodof up to about 50 ms after the stimulation. Any change in thecharacteristics of the QRS complex 130 following delivery of thesubpacing pulse at delivery point 110 can be used in the diagnosis of apatient's susceptibility for arrythmia and cardiac tissue abnormality. Adesired pulse position with respect to a detected R-wave is configuredby the operator. When the intended position and time with respect to adetected R-wave is at or following the R-wave, then the device deliversa pulse after an appropriate-length delay following the most recentlydetected R-wave. When the intended position and time with respect to adetected R-wave are before the R-wave, then the device uses the previousR-interval 144 to determine an estimated time for delay by subtractingthe desired amount from the R to R interval 144. The device thendelivers the pulse after the determined delay following the mostrecently detected R-wave. The computer software is controlled withsimulation and data acquisition during testing. During each test, thesoftware delivers stimulation to alternating QRS complexes, based onrealtime R-wave detection. Signals are recorded from lead system 12,along with the stimulation and R-wave detection locations. This ismonitored and is terminated when the appropriate number of pulses havebeen delivered in the region identified in the test parameters.

[0111] Another process for arrythmia detection is that of t-wavealternan analysis. This process involves looking for alternations frombeat to beat in the signal produced during the t-wave portion of theheart signal. The t-wave is the portion of the heart signal that followsthe QRS “contraction” (see FIG. 31) of the heart. The QRS area is calleddepolarization. The t-wave is called repolarization because the cellsare electrically preparing for the next depolarization. T-wave analysisinvolves computing the ‘power’ of each t-wave and looking foralternations in this power from beat to beat. This phenomenon tends toincrease in people prone to arrhythmia. The use of t-wave alternananalysis with the previously-described technique of subthresholdstimulation is anticipated by this invention.

[0112] An overview of the operation of this invention can be seen inFIG. 33. Sensing Leads 202 pass received Signals 248 to thefast-recovery amplifier, at which time the Signals 248 are passed to theAnalog to Digital converter 208. Thereafter, Data 250 is used todetermine R-wave Detection 237 and for LEM modeling 215. Data 250 isalso capable of going to Storage 218, and is further used forPost-Processing 240, where data 250 is eventually displayed to computermonitor 23. During the fast-recovery amplifier stage 254, BlankingControl 212, through Control 253, is used to compensate for blanking.This blanking control is initiated through the Software and HardwareControl Logic 234 via Control 253. Control 259 controls the R-wavedetection 235 as it is passed to the Software and Hardware Control Logic234. Software and Hardware Control Logic 234 further controls a ShuntControl 225 via Control 254; and Control 257 controls Current ControlledDriver 221. Hardware and Software Control Logic 234 passes Data 250 tothe Digital to Analog Conversion 228, thereafter passing those Signals255 to the Current Controlled Driver 221. At the appropriate time,Signal 255 is delivered to Stimulation Leads 206. Post-Processing 240also performs LEM modeling 215, Digital Filtering 243, and StatisticalCalculations 246, described in more detail below.

[0113] A significant part of the subject invention is the amplifier anddriver circuitry located in electronic interface 18. Electronicinterface 18 provides amplification of signals received from lead system12 and amplifies those signals to a level of impedance readable by thecomputerized data acquisition/control system, such as computer 27.Electronic interface 18 also takes control signals from the computerizeddata acquisition/control system, such as computer 27, and providesstimulation into lead system 12, as described above. The amplifiercircuitry is designed to record lead signals that occur immediatelyfollowing the injection of energy into the lead system. The recordingtypically occurs within only several milliseconds of the injection ofenergy. Fast recovery is important to the system because of the need tosense electrical information very shortly after a stimulation. In onepreferred embodiment shown in FIG. 37, each vector X, Y, and Z has itsown amplifier, X amplifier 155, Y amplifier 165, and Z amplifier 175.Stimulator 180 controls subpacing pulse delivery in conjunction withcomputer 27; and the software Power Conditioning Circuit 182 powersamplifiers 155, 165, and 175 supplying Stimulator 180 with subpacingcurrent. FIG. 38 is a wire-level diagram of FIG. 37, illustrating thisadvantageous design.

[0114] To provide for such fast recovery, several methods are employed.The sensing leads are comprised of fast-recovery material, such as tin,sodium, silver and silver chloride, or other such material know to thoseskilled in the art, to facilitate rapid dissipation of any energyinduced by the system. Further, electronics interface 18 uses amultistage amplification scheme as known to those persons skilled in theimplementation of amplifiers, with improvements for fast recovery. FIG.38 shows a wire-level block diagram of this embodiment of electronicinterface 18. In one preferred embodiment, electronic switches areplaced between amplification stages, which are used to decouple stageswithin the amplifier. The amplifier must be switched into itshigh-impedance mode, with appropriate time allowances for all electricalswitching to be completed prior to the application of any energy to thestimulation leads. Similarly, when switching back to normal impedancemode, appropriate timings must be used to ensure that all stimulationenergy is completely terminated prior to lowering the amplifierimpedance. This timing must account for any engaging or disengagingdelay in both the amplifier and energy delivery circuits. When theamplifier is in its normal- or low-impedance mode, it has a capacity tostore up charge in a very short period of time. Therefore, applicationof stimulation energy, however short, in this mode will greatly increaseundesirable artifact. Therefore, timing is critical in decoupling theamplifier to reduce artifact. Advantageously, switch timing issoftware-controlled in one preferred embodiment of this invention. Othertiming means are known to those skilled in the art. Filtering isimplemented by this invention to filter the acquired signal to eliminatepossible high frequency, switch-related artifacts.

[0115] An additional clamping circuit is also employed to aid in thereduced recovery time during stimulation. As can be seen in FIG. 39, anelectronic track and hold switch 160 is placed between two stages of theamplifier. Track and hold switch 160 remains closed during stimulation,and in a preferred embodiment, a blanking period following stimulation.FIG. 39 is a block diagram/flow chart of the operation of the isolatedfast-recovery EKG amplifier.

[0116] Differential input signal 261 enters the Differential First StageAmplifier Circuitry 264. The signal is thereafter controlled by ClampingCircuit 117. The signal is then conditioned by Bandpass Gain Stage 267and is regulated by Impedance Switching Track and Hold Circuitry 160. Asdepicted in FIG. 39, Switch Control 277 and Switch Isolation circuitry275 control the timing of the signal. At the appropriate time, signalspass to Low Pass circuitry 269 and then to Final Gain Stage 271 andIsolation Stage 273. Finally, the amplified signal leaves thefast-recovery EKG amplifier as Amplified Signal 278.

[0117]FIG. 40 is a schematic of the fast-recovery EKG amplifier. FIG. 40depicts the circuitry implementing the flow chart of FIG. 39. As can beseen, differential inputs 183 connect to the differential first-stageamplifier circuitry 187. The next stage is clamping circuitry 184, whichis in electrical communication with the bandpass gain stage 185. Nextare the switch-and-hold circuitry 181, low-pass filter stage 189, andfinal gain stage 188. Isolated circuitry 186 and switching circuitry 181are also depicted in FIG. 40.

[0118]FIG. 32 is a block diagram of the switching circuit. A clampingcircuit is also added within the preswitch stages. The clamping circuitis designed to engage when the input signal is greater than about plusor minus 5 mV. When switch 70 is closed, the circuit behaves as atypical amplifier, using the reference lead as a body surface referencepoint for amplification of the differential signal between the positiveand negative leads. Advantageously, this reference point is utilizedduring periods of blanking of the input signals. The clamping circuitremains inactive for input signals of plus or minus 5 mV. This allowsamplification of normal skin surface ECG signals. During stimulation,the switch electronically disengages the amplification stages from eachother. While open, switch 70 itself provides a hold function that holdsconstant the signal level for all postswitch stages 74. Switch 70 alsodecouples the reference signal from the preswitch stage 77. Thisdecoupling advantageously prevents the preswitch stage from acceptingany transient energy present during stimulation. In addition, to switch70, clamping circuit 62 engages when the input signal of greater thanplus or minus 5 mV occurs. This clamping circuit 62 uses reference lead9 to measure a baseline. A baseline shift is caused by the remnantcharge left in the patient's body following the stimulation, shuntingand modeling cycles performed by a preferred embodiment of theinvention. This remnant charge equalizes over time at an exponentialrate referred to as baseline decay. Compensation for baseline effectscan be done by subtracting a non-stimulated waveform from a stimulatedwaveform. Further, a baseline shift with a time constant decay may alsobe utilized. The decay rate may be modeled by sampling the decay rateover a predetermined interval, for example, about 10 ms. The decayingbaseline shift can then be mathematically removed from the acquireddata. Advantageously, the decaying baseline shift may be removed forpredetermined intervals, for example, intervals up to about 300 ms.Baseline noise can advantageously be reduced by filtering andstatistical noise reduction by this invention. Whenever the input signaldeviates from this baseline by more than 5 mV, the internalamplification stage is held at that level. This further reduces theeffect of transient voltages generated during stimulation. These twofeatures work together to keep the amplifier stages as close as possibleto their prestimulation values, advantageously providing a very fastrecovery time. An additional circuit in postswitch stage 74 provides afilter that eliminates any possible high-frequency, switch-relatedartifact that may occur. This is required because of the nature of theswitch employed. This recovery technique is incorporated within theamplifier in one preferred embodiment of this invention.

[0119]FIG. 41 is a flow chart/block diagram of the isolated driversection of the subject invention. This is additional circuitry locatedwithin electronic interface 18. This driver section depicted in FIG. 41has the characteristics to shape the energy delivery pulse to reducerise-and-fall slopes, thereby reducing induced artifact signals.Further, the isolated driver depicted in FIG. 41 provides for shuntingof any charges built up as a result of energy delivery. Shunting meansmay include switching from a high-impedance path to a low-impedance pathfor a short period of time to dissipate unwanted voltage that ispresent. The switching between high and low impedances is designed tooccur within a time of less than 1 ms. Typically, high impedance isgreater than about 5,000 Ohms, and low impedance is less than about 500Ohms. This shunting means can be connected between more than one energydelivery lead. Further, the driver employs a constant current circuit,thereby allowing control over energy delivery and varying lead orphysiological impedances. As can be seen from FIG. 41, the CurrentControl 197 communicates with Isolated Driver Circuitry 193.Advantageously, there is also safety circuitry, which includes SafetyFuse 199 and Isolated Safety Relay 198, controlled by Safety RelayControl 192. Shunt Control 196 then controls the Isolated ShuntCircuitry 170, which timely delivers the subpacing current output 194 tothe subject.

[0120]FIG. 42 is a schematic level of an exemplary isolated driversection. Blocked off on the schematic are Isolated Driver section 193,Safety Fuse 172, safety switch 174, and shunting circuitry 170.

[0121] Additional techniques and means for improving sensing andanalysis of cardiac signals will now be discussed, including bothstimulated as well as non-stimulated signals. Such techniques and meansinclude: wavelet decomposition, alternative or passive shunting,detection of ECG alternans, stimulation of alternans behavior, detectionof differences between natural and stimulation induced alternansbehavior, cardiomyopathy detection techniques, body surface shuntingsynchronous with the R-Wave on Signal Averaged Electrocardiogram,subthreshold stimulation without capture to reduce the stimulationthreshold causing changes to the action potential of a subsequentsuprathreshold stimulation with capture, Wedensky transthoracicstimulation, Wedensky phenomenon within the late potential region,wavelet analysis of subthreshold stimulated and control Signal AveragedElectrocardiograms in healthy subjects and ventricular tachycardiapatients, QRS complex alternans detected by wavelet decomposition ofSignal Averaged Electrocardiograms, and QRS background noisedifferentiation. Each such means will now be discussed, includingreference to FIGS. 47-57.

[0122] Wavelet Decomposition is a mathematical analysis allowing thestudy of a particular signal of interest in the presence of othersignals. The analysis allows itself to be tuned towards highersensitivity to one or more particular type(s) of waveforms whilereducing sensitivity towards another. This type of analysis isparticularly useful when used on ECG data. ECG data can contain specificenvironmentally present electrical noise, for example 50 Hz or 60 Hz.ECG data may also contain broadband constant or intermittent noiseproduced by local sources of electromagnetic interference. The dynamicsof the ECG waveform itself (as it is produced by the heart) can bedefined in both frequency and amplitude. Research has defined such ananalyzing waveform for use with Wavelet Decomposition in studying ECGdata. This application includes the use of such wavelet decomposition toanalyze either the natural ECG or stimulated ECG data produced by an ECGdevice, including the devices disclosed herein. Also included is the useof wavelet decomposition to analyze combinations of natural ECG orstimulated ECG data produced by an ECG device, including the devicesdisclosed herein.

[0123] This application discloses, inter alia, the methods and apparatusof using the stimulation electrodes (or any large area surfaceelectrodes) in an ECG device, including the devices disclosed herein, asa method of enhancing sensing of cardiac condition. First, theseelectrodes can act as a shielding mechanism to enhance the sensing ofECG signal. The presence of a large area electrode acts as an electricalshield allowing better sensing of cardiac signal. The use of such anelectrode is identified and claimed here.

[0124] Shunting is a technique of dissipating unwanted voltage. Use ofthe devices and methods disclosed herein involve the delivery of energyfollowed by the shunting of the stimulation leads as a means of reducingthe artifact caused by charge remaining on the lead system. Thisshunting process also has application when no energy is deliveredthrough the leads, and is interchangeably referred to herein asalternative or passive shunting.

[0125] By passively changing (shunting) the potential of a large area ofthe body, an impedance modulation in the body can be realized. Thegeneration of the surface ECG from the heart involves the current flowfrom cell to cell as depolarization recruitment progresses. This currentvector multiplied times the local resistivity gives the local electricalfield. The components of that on the skin are what is called the ECG. Bypulsing the shunt across the chest it is possible to modulate thatresistance (i.e., “impedance modulation”). This is similar to changingthe angle of view of the cardiac signal. This altered measurement canalso be compared against the non-shifted measurement.

[0126] Also disclosed herein is the process of shunting these or anylarger area surface electrodes together to effectively provide anisopotential at the skin surface. This action can be viewed as “passivestimulation.” It can shift the body potentials and possibly alterconduction pathways to allow better sensing of the cardiac condition.This altered measurement can also be compared against the non-shiftedmeasurement. The use of either “impedance modulation” or “passivestimulation” and its effect on the QRS signal is thus disclosed herein.

[0127] Alternant behavior consists of the changing of cardiac signal ina modal fashion. That is, one beat will have certain characteristics,the next will have different characteristics, and the following willhave characteristics like the first. The process of averaging togetheralternate beats used in an ECG device, including the devices disclosedherein, allows the measurement of the natural ECG alternan behavior. Theextent and change of this measurement can be a measure of cardiaccondition. The use of this measurement as an indication of cardiaccondition is disclosed and included in this application.

[0128] By averaging together alternate beats, the systems and methodsdisclosed herein allow the measurement of alternan behavior. This methodcan be useful in the determination of cardiac condition. Thus, thisapplication discloses use of the systems and methods to achievestimulation-related changes in alternan behavior, or shunting/impedanceshifting-related changes (passive stimulation in alternan behavior as amethod for detecting cardiac condition). Furthermore, the differencesbetween natural alternan behavior and stimulated alternan behavior canalso be useful in determining cardiac condition. This applicationdiscloses and includes the use of the differences between thesebehaviors as an indicator of cardiac condition.

[0129] A further use of the devices and methods disclosed herein is toassess conduction pathway changes within the heart by examining thechanges in ECG while stimulating and not stimulating the myocardium.Another use disclosed herein is to detect non-conduction relatedabnormalities of the heart including, but not limited to,cardiomyopathy. The changes invoked by the process of stimulating,shunting, or examining alternate beats could also be used to determinethe extent of physical myocardial abnormality. Stimulation relatedchanges, shunting and impedance shifting related changes (passivestimulation), or changes due to average of alternate beats as a methodof detecting non-conduction related abnormalities are disclosed andincluded herein.

[0130] Applicants have further discovered improved means for signalanalysis by analyzing the effect of body surface shunting synchronouswith the R-wave on Signal Averaged Electrocardiograms by comparing thedifferences between normal subjects and patients with ventriculartachycardia. This study investigated the effects of creating a bodysurface short circuit synchronous with the R-wave on the spectralprofile of signal averaged electrocardiograms.

[0131] In 35 patients with EP inducible ventricular tachycardia and in30 healthy volunteers, 60 to 200 QRS complexes were digitally recordedusing orthogonal leads. Synchronous with on-line R-wave detection, twosurface patches corresponding to the orthogonal Z lead (a precordialpatch and a left dorsal subscapular patch) were electrically connectedwith negligible impedance for 2 ms. The QRS complexes recorded in thisway were averaged and compared with the same number of averaged QRScomplexes recorded without surface shunting. Both high-gain signals weredecomposed with 53 scales of Morlet wavelets of central frequencies 40to 250 Hz and vector magnitudes of wavelet decompositions wereconstructed. The differences between these decompositions werecharacterized by their surface areas in windows of 0 to 10 ms, 10 to 20ms, and 20 to 30 ms, etc., after surface shunting.

[0132] The area difference was substantially greater in healthyvolunteers, as shown by the light bars in FIG. 47, than in VT patients(dark bars) both immediately, i.e., 0-10 ms after surface shunting(p<0.04) and 10 ms later (p<0.03) but not later (p=0.4 at 20 ms later,and p=0.5 at 30 ms later). From this research data, it may be concludedthat short circuiting the body surface produces both recording artifactand physiological stimulus affecting the depolarization sequence. Thisstimulus is very short lived and is more marked in healthy hearts thanin VT patients who are probably less susceptible to minor electricalprovocations.

[0133] Applicants further compared high-gain electrocardiographicevidence of Wedensky Phenomenon in healthy subjects and ventriculartachycardia patients. Of course, it is known that Wedensky Phenomenon isthe effect of a subthreshold stimulation without capture that reducesthe stimulation threshold and changes the action potential of asubsequent suprathreshold stimulation with capture.

[0134] To investigate whether this phenomenon can be documented aftertransthoracic subthreshold stimulation (2 ms. pulse of 5 to 40 MAbetween surface precordial and subscapular patches delivered synchronouswith R-wave detection), 60 to 200 subthreshold stimulated QRS complexeswere signal averaged and compared with the same number of averagenon-stimulated complexes recorded during the same experimental session.The electrocardiographic recordings were obtained with standardorthogonal leads. In order to detect even minor changes within the QRScomplex, each lead of both stimulated and control averaged complexeswere wavelet decomposed (53 scales of the Morlet wavelet with centralfrequencies of 40 to 250 Hz). The wavelet residuum corresponding to theWedensky Phenomenon was obtained by subtracting the vector magnitudewavelet decomposition of the control QRS from the vector magnitudedecomposition of the subthreshold stimulated QRS. The surface of theresiduum was investigated in windows of 1 to 25 ms following thestimulation. The test was performed in 35 patients with EP inducibleventricular tachycardia and in 30 healthy controls.

[0135] The wavelet residuum showed sharp increase in the spectral powerof the stimulated complex that was significantly more marked in healthyvolunteers (p<0.01) than in VT patients. This is shown in FIG. 48, inwhich there is 20 ms stimulation, and in which full circles are VTpatients, and empty circles are control patients. This shows thatWedensky phenomenon induced by an external transthoracic subthresholdstimulation can be documented in man and differentiates VT patients fromcontrols.

[0136] In further investigation, patients with electrophysiologicdocumented ventricular tachycardia (n=35) and healthy controls (n=30)were subjected to a subthreshold external stimulation between precordialand left subscapular patches. Stimuli of 5, 10, 20, and 40 ma weredelivered for 2 ms synchronous with R-wave detection. 60 to 200subthreshold stimulated QRS complexes were averaged and compared withthe same number of non-stimulated complexes. Vector magnitude waveletdecompositions (53 scales of central frequencies 40 to 250 Hz) wereobtained for both stimulated and non-stimulated complexes and theirdifference characterized the Wedensky Phenomenon numerically. Thesurface area of the 3D envelope of the wavelet residuum was measured ina window ±5 ms from the R peak (stimulation moment) and in surrounding10 ms windows.

[0137] The wavelet residuum showed a sharp increase of the surface ofthe 3D spectral envelope at and after the stimulation that was moremarked in healthy volunteers than in VT patients, as shown in FIG. 49 inwhich 40 ma experiments were conducted, and full circles are VTpatients, and open circles are control patients. The maximum changes inwavelet residuum increased with stimulation subthreshold energy: 5 ma:control 1993±181 technical units, VT patients 1488±159; 10 ma: control2151±200, VT patients 1543±154; 40 ma: control 2746±332, VT patients1842±177, i.e., all were statistically significant. Thus, externallyinduced Wedensky phenomenon shows a dose response that is more marked inhealthy volunteers than in VT patients.

[0138] Wedensky Phenomenon within the late potential region was analyzedutilizing dose-related separation of patients with ventriculartachycardia from healthy controls. Patients with EP documentedventricular tachycardia (n=35) and healthy controls (n=30) weresubjected to a subthreshold external stimulation between precordial andleft subscapular patches. Stimuli of 5, 10, 20, and 40 ma were deliveredby 2 ms after a 20 ms delay following a realtime R-wave detection. 60 to200 subthreshold stimulated QRS complexes were averaged and comparedwith the same number of non-stimulated complexes. Vector magnitudewavelet decompositions (53 scales of central frequencies 40 to 250 Hzwere obtained for both stimulated and non-stimulated complexes and theirdifference characterized the Wedensky Phenomenon numerically. Thesurface area of the 3D envelope of the wavelet residuum was measured ina window 20±5 ms after the R peak (a window centered around thestimulation moment) and the subsequent 10 ms windows (30±5 ms after theR peak). The areas of the residuum spectral 3D envelope in these windowswere statistically compared in the VT patients and healthy controls.

[0139] All differences were highly statistically significant, as shownin FIG. 50 (up to p<0.00005), with the manifestation being morepronounced in the control group. The separation of the groups was moresignificant in the window around the stimulation moment that in thesubsequent window and the significance decreased with increasingsubthreshold stimulation energy. Accordingly, a Wedensky phenomenon inthe late QRS part is brief, and VT patients are less sensitive to thephenomenon, especially at very low subthreshold energies.

[0140] In yet another assessment, patients with EP documentedventricular tachycardia (n=35) and healthy controls (n=30) weresubjected to a subthreshold external stimulation between precordial andleft subscapular patches. Stimuli of 5, 10, 20 and 40 ma were deliveredfor 2 ms either simultaneously with the R-wave or 20 ms after theR-wave. 60 to 200 subthreshold stimulated QRS complexes were averagedand compared with the same number of non-stimulated complexes(reference). Vector magnitude wavelet decompositions (53 scales ofMorlet wavelet with central frequencies 40 to 250 Hz) were obtained forboth stimulated and non-stimulated complexes. Local maxima of the 3Dspectral envelopes were counted in 50 ms windows following thesubthreshold stimulation and compared in VT patients and healthycontrols.

[0141] In reference recordings, FIG. 51, there were no statisticaldifferences between VT patients (shown as closed dots) and controls(open dots). In subthreshold stimulated recordings, the local maximadecreased (3D spectral envelopes became more smooth). This decrease wasgreater in healthy controls and with stimulation after the R-wave, FIG.52, wherein all the differences except in experiment {fraction (10/00)}were significant up to p<0.001. Accordingly, subthreshold externalstimulation makes the depolarization wave more uniform, mainly whendelivered in the terminal QRS part in healthy volunteers.

[0142] Although the electrical altemans of the ST segment and T-wave hasbeen extensively researched, the alternans of the QRS complex hasgenerally not been investigated mainly because of difficulties indetecting it. Applicants' innovations overcome such previouslimitations, and allowed further assessment as follows.

[0143] In 35 patients with EP inducible ventricular tachycardia and in30 healthy volunteers, 120 to 400 QRS complexes were digitally recordedusing orthogonal leads. From these sequences of beats, the complexeswith even and odd order numbers were separately aligned and averaged.The resulting high-gain signals were processed with waveletdecomposition (53 scales of Morlet wavelets with central frequencies of40 to 250 Hz) and the differences between the resulting 3D spectralenvelopes were computed. These created alternans-related 3D spectralenvelopes and were characterized by surface areas in subsequent 10 mswindows.

[0144] The surfaces of the alternans-related 3D spectral envelopes weresubstantially larger, as shown in FIG. 53, in VT patients (full circles)compared to healthy controls (open circles). The differences between thegroups were particularly marked within the initial and terminal portionsof the QRS complex (p<0.00005 in the 10 ms window preceding the R-waveby 40 ms). Thus, a wavelet decomposition of alternating signal averagedECG is capable of detecting electrical alternans within the QRS complex,and the QRS complex alternans is significantly more expressed in VTpatients compared to healthy controls. Also, the QRS complex alternansdiffers between VT patients and controls mainly at the beginning and atthe end of the QRS complex.

[0145] Of the many improvements discussed above, it is worth noting thatwavelet analysis is particularly significant. Indeed wavelet analysis isa highly reproducible method for SAECG processing which is as powerfulas the time-domain analysis for the identification of ischemic VTpatients. As compared to the time-domain analysis, wavelet analysis isnot dependent on infarct site, and is able to distinguishpost-myocardial infarction patients without VT from healthy subjects. Ascompared to known applications of wavelet representations, Applicantsutilized much finer distinctions of scales (7 vs. 54) with a differentrange of middle frequencies (70-200 Hz vs. 40-250 Hz). Applicants alsodetermined that wavelet analysis of signal-averaged ECGs is superior tothe standard time-domain analysis in predicting post myocardialinfarction events. In particular, this analysis identifies not onlythose post MI patients who are at risk of non-fatal sustainedventricular tachycardia, but also those who are at risk of suddencardiac death. Thus, this is the first discovery of using waveletanalysis for categorical risk analysis with prospectively collectedsignal-averaged ECG data in an almost consecutive population of MIsurvivors. As such, a significant advantage of this technology is thatcompared with standard time-domain analysis, the wavelet decompositionof signal-averaged ECGs provides a more powerful distinction betweensurvivors of an acute MI who are and are not at high risk of furthercomplications. FIG. 54 shows sample data of the interdependence oftime-domain and wavelet decomposition indices, in which is presented thecorrelation coefficient between the two techniques. The value ofcorrelation coefficient is shown above the diagonal, and thecorresponding p-values are displayed below. FIG. 55 is data representinga comparison of signal-averaged ECG indices in patients with and withoutfollow-up events. For each category of follow-up events and for eachtime-domain and wavelet decomposition parameters, the table lists theaveraged value in patients with and without the event. The last column(p=) shows the significance of statistical comparison of values inpatients with and without events (nonparametric Mann-Whitney test). FIG.56 shows the association of positive SAECG findings with follow-upevents. For each category of two year followup events and for each offour diagnostic criteria, the table shows the number of true positive(tp) and true negative (tn) patients as well as the statisticalsignificance (p—) of the association of events with findings of apositive signal averaged ECG analysis (Fishers exact test). Herein, CMrepresents cardiac mortality, PAD represents potentially arrhythmicdeath, SCD represents sudden cardiac death, VT represents sustainedventricular tachycardia, PAE represents potentially arrhythmic events,and ARF represents sudden cardiac death and/or ventricular fibrillation.FIG. 57 is a comparison of positive predictive accuracy of predictingfollow-up events. In this figure, for each category of follow-up eventsand for six selected levels of sensitivity (Sen), the table showsmaximum positive predictive accuracy (PPA) achieved at that level ofsensitivity with time-domain indices (TD) and wavelet decompositionindices (WD) of signal averaged ECGs. The table also shows the numbersof patients for which the diagnostic criteria of both techniquesadjusted for the given level of sensitivity did not agree (Discordance)divided into the number of those for which the time-domain diagnosis wascorrect (TD+) and those for which the wavelet decomposition diagnosis(WD+). The last column shows the statistical significance (p=) of thecomparison of values of TD+ and WD+ (sign test).

[0146] One additional signal improvement technique involves improvednoise management in the QRS realm. When sensing signals from electrodes,a certain amount of environmental background noise is unavoidable. Thisnoise may vary in frequency and direction, causing certain electrodeplacements to be more sensitive to receiving it than others. Thefollowing software-based approach addresses an implementation to reducesensitivity to this background environmental noise during the processingof data recorded from electrodes.

[0147] To improve alignment of QRS complexes of multiple channel ECGdata (XYZ, multi-lead intercardiac, 2 lead, etc.) a mechanism whichreduces sensitivity to background noise may be applied. The mechanisminvolves the determination of the signal level of the background noiseand the signal level of the desirable signal (in the case of ECG data,the QRS). These parameters are determined for each data channel. Theparameters are combined into ratios of Desirable/Background signals(hereby called D/B ratio). Channels with low D/B ratios are excludedfrom use during QRS alignment. Since it is possible for background noiseto vary over time, an alternate implementation of this mechanism couldbe to assess the signal around each QRS complex for D/B ratio andexclude QRS's based on their individual ratios.

[0148] While the invention has been described in conjunction withspecific embodiments thereof, it is evident that many alternatives,modifications, and variations will be apparent to those skilled in theart in light of the foregoing description. Accordingly, it is intendedto embrace all such alternatives, modifications, and variations whichfall within the spirit and broad scope of the invention.

What is claimed:
 1. A method for assessing heart characteristicscomprising the steps of: connecting a lead system to a patient's bodyfor sensing cardiac signals, the lead system comprising energy sensingleads; sensing and storing a first set of cardiac signals via the leadsystem; passively altering an impedance of the patient's body as sensedby the lead system to alter at least one set of cardiac signals; sensingand storing a second set of passively altered cardiac signals via thelead system; and comparing the second set of passively altered signalswith the first set of signals.
 2. The method of claim 1, in which thestep of passively altering the impedance of a patient's body comprisesthe steps of operably electrically connecting electrodes to thepatient's body and shunting the electrodes together.
 3. The method ofclaim 2, in which the electrodes are large area electrodes.
 4. Themethod of claim 2, in which the electrodes have a skin contact surfacearea of between about twenty square centimeters and about seventy squarecentimeters.
 5. The method of claim 2, in which the electrodes areattached to a ventral surface of the patient's torso and a dorsalsurface of the patient's torso.
 6. The method of claim 2, in which theelectrodes are attached to the pectoral region and the back.
 7. Themethod of claim 2, further comprising the step of timing the shunting ofthe electrodes to occur during a PQ interval.
 8. The method of claim 2,further comprising the step of timing the shunting of the electrodes tooccur shortly prior to a QRS complex.
 9. The method of claim 2, in whichthe electrodes are shunted together prior to every other QRS complex.10. The method of claim 1, in which the step of passively altering theimpedance comprises controlling the potential of a large surface areaelectrode.
 11. The method of claim 10, in which the electrode has a skincontact surface area of between about twenty square centimeters andabout seventy square centimeters.
 12. The method of claim 1, in whicheach of the sensing and storing steps further includes electronicallyimproving the quality of the sensed cardiac signals prior to storing thecardiac signals.
 13. The method of claim 12, in which waveletdecomposition analysis is used to electronically improve the quality ofthe cardiac signals.
 14. A device for detection of a patient'ssusceptibility to arrhythmias, the device comprising: a lead system forsensing cardiac signals, the lead system comprising energy sensingleads; means for sensing and storing a first set of cardiac signals viathe lead system; means for passively altering an impedance of apatient's body as sensed by the lead system to alter at least one set ofcardiac signals as sensed by the leads; means for sensing and storing asecond set of passively altered cardiac signals; and means for comparingthe first set of signals with the second set of signals.
 15. The deviceof claim 14, in which the passive altering means comprises electrodeselectrically connected to the patient's body, the electrodes beinginterconnected so as to be shuntable together.
 16. The device of claim15, in which the electrodes are large area electrodes.
 17. The device ofclaim 15, in which the electrodes have a skin contact surface area ofbetween about twenty square centimeters and about seventy squarecentimeters.
 18. The device of claim 15, in which the electrodes areattachable to the ventral surface of a torso and a dorsal surface of thetorso.
 19. The device of claim 15, in which the electrodes are attachedto a pectoral region and a back.
 20. The device of claim 15, in whichthe passive altering means is adapted to shunt the electrodes during aPQ interval.
 21. The device of claim 15, in which the passive alteringmeans is adapted to shunt the electrodes shortly prior to a QRS complex.22. The device of claim 14, in which the means for passively alteringthe impedance comprises controlling the potential of a large surfacearea electrode.
 23. The method of claim 22, in which the electrode has askin contact surface area of between about twenty square centimeters andabout seventy square centimeters.
 24. The method of claim 22, in whichthe means for sensing and storing further comprises sensing improvementmeans for improving the quality of the sensed electromagnetic energyduring the sensory process.
 25. The method of claim 24, in which thesensing improvement means comprises wavelet decomposition analysis. 26.A device for detection of a patient's susceptibility to arrhythmias, thedevice comprising, a lead system for sensing sets of cardiac signals,the lead system comprising energy sensing leads; an electrodecontrollable to passively alter an impedance of a patient's body, assensed by the lead system, so as to alter some of the sets of cardiacsignals; circuitry to sense and store the sets cardiac signals; andmeans for comparing the cardiac signals altered by passive stimulationwith unaltered cardiac signals.
 27. The device of claim 26, in which theelectrode comprises at least two electrodes electrically connected tothe patient's body, the electrodes being interconnected so as to beshuntable together.
 28. The device of claim 27, in which the electrodesare large area electrodes.
 29. The device of claim 27, in which theelectrodes have a skin contact surface area of between about twentysquare centimeters and about seventy square centimeters.
 30. The deviceof claim 27, in which the electrodes are attachable to the ventralsurface of a torso and the dorsal surface of a torso.
 31. The device ofclaim 27, in which the electrodes are attached to a pectoral region anda back.
 32. The device of claim 26, in which the controllable electrodefurther comprise a timing circuit adapted to shunt the electrodes duringa PQ interval.
 33. The device of claim 26, further comprising a timingcircuit adapted to shunt the electrodes shortly prior to a QRS complex.34. The device of claim 26, further comprising a circuit for controllingthe potential of a large surface area electrode.
 35. The method of claim26, in which the circuitry to sense and store further comprises waveletdecomposition analysis of the cardiac signals prior to storing thecardiac signals.